The blood clotting process consists of several of the most important types of reactions in protein chemistry, viz., enzymatic steps (proteolysis, transamidation, etc.) and protein association. In this project, we are concentrating on the proteolytic action of thrombin on fibrinogen. We thus hope to contribute to an understanding of the mechanisms of this fundamental protein reaction, as it is involved in the blood clotting process, and, at the same time, to provide a basis for treating many of the cardio-vascular problems involving blood clotting (e.g., heart failure, stroke, hemophilia, etc.). Bibliographic references: H.A. Scheraga - Theoretical and Experimental Aspects of the Mapping of Active Sites of Enzymes, in Table Ronde Roussel UCLAF on "The Active Sites of Enzymes" (R. Acker, D. Arigoni, and D.C. Phillips), Paris, December 4, 5, 1974, p. 30. G.F. Endres, M.K. Swenson and H. A. Scheraga - Structural Aspects of Thrombin Specificity, Arch. Biochem. Biophys., 168, 180 (1975).